雷公藤心肝肾毒性的风险分析与机制探讨  

Risk Analysis and Mechanism Discussion of Cardiovascular,Hepatic,or Nephrotoxicity Induced by Tripterygium Wilfordii

作　　者：陈莉娟 张晓朦[1,2] 高福君 刘泽宇 王雨 张冰[1,2] CHEN Lijuan;ZHANG Xiaomeng;GAO Fujun;LIU Zeyu;WANG Yu;ZHANG Bing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Center for Pharmacovigilance of Chinese Materia Medica Research,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京中医药大学中药药物警戒与合理用药研究中心,北京102488

出　　处：《中国药物警戒》2024年第11期1224-1231,共8页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(82204643、82274117);中央高校基本科研业务费专项资金(2024-JYB-JBZD-054)。

摘　　要：目的以雷公藤为例分析其药源性心、肝、肾不良反应/事件(ADR/ADE)的发生特点与潜在机制,为临床合理用药提供参考。方法回顾收集从建库至2024年1月1日的中国知网中关于雷公藤导致心、肝、肾ADR/ADE临床个案报道,采用Apriori关联分析与决策树CART算法,分析其造成心、肝、肾毒性的原因。基于中药系统药理学分析平台、GeneCards数据库等收集雷公藤所含化合物及心、肝、肾作用靶点,采用网络药理学分析其导致多脏器毒性的内在机制。结果共收集到雷公藤导致心、肝、肾ADR/ADE 50例,其中累及2种及以上系统-器官20例,造成心、肝、肾毒性与服药剂量、疗程的关联性较强,与患者原患疾病亦有一定关联。筛选出雷公藤化合物51个,有效作用靶点153个。通过Venn图获得987个心、肝、肾毒性共同靶点,PPI网络和GO功能分析揭示了TP53介导的细胞凋亡、AKT1及STAT3介导的炎症反应等过程可能与雷公藤的心、肝、肾多脏器毒性相关。结论雷公藤造成多脏器毒性有着内在关联,有待深入研究,临床需要严格控制用药剂量与疗程。Objective To analyze the characteristics and potential mechanisms of adverse drug reactions/events(ADR/ADE)in the heart,liver,or kidney caused by Tripterygium wilfordii(Leigongteng),with the aim of providing reference for the rational use of medicine in clinical practice.Methods The ADR/ADE in the heart,liver,or kidneys caused by Leigongteng were collected retrospectively from the China National Knowledge Infrastructure(CNKI)from constrac tion to 1,Jan 2024.By using Apriori association analysis and decision tree CART algorithm,the influencing factors that caused by Leigonteng to the heart,liver,or kidneys damage were conducted.After collectting the compounds contained in Leigongteng and the action targets of the heart,liver,or kidneys based on the Traditional Chinese Medicine Systems Pharmacology Analysis Platform and GeneCards database,using network pharmacology to analyze the intrinsic mechanisms of Leigongteng’s multi-organ toxicity.Results A total of 50 cases ADR/ADE involved the heart,liver,or kidneys damage were collected,among which 20 cases involved two or more systems-organs.There was a strong correlation between the toxicity to the heart,liver,or kidneys and the dosage and duration of medication,and there was also a certain association with the patient’s original diseases.51 compounds from Leigongteng and 153 effective action targets were screened out.Through the use of Venn diagrams,987 common targets of toxicity to the heart,liver,and kidneys were identified.Protein-protein interaction network and Gene Ontology functional analysis revealed that TP53-mediated apoptosis,AKT1 and STAT3-mediated inflammatory responses may be associated with the multi-organ toxicity of Leigongteng to the heart,liver,and kidneys.Conclusion The multi-organ toxicity caused by Leigongteng has intrinsic correlations that require further in-depth research,and clinical prevention necessitates strict control over the dosage and duration of medication use.

关 键 词：雷公藤 风险分析 心 肝 肾 风险机制 药物警戒 

分 类 号：R994.11[医药卫生—毒理学]